In the field of pharmaceuticals, oral dosage forms of drugs are a preferred method of delivery for a variety of reasons. Generally, active pharmaceutical ingredients (APIs) supplied, in oral dosage form are easier to manufacture, dispense and administer. Manufacture is made simpler and more consistent due to the existence of well-established techniques for producing consistent doses in forms that can be chemically very stable. Dispensing and administration are simpler since oral dosages can typically be self-administered, as opposed to other forms such as intravenously supplied drugs, which are more difficult to administer, or which may require a trained professional in order to properly administer to a patient in need of the therapeutic moiety.
Recently, advances in chemistry and drug design methodologies have led to the discovery of a number of new drug candidates. For example, high throughput screening and combinatorial chemistry are very efficient at selecting candidate drugs based on specific binding to a target of interest. Target specificity is highly desirable in therapeutic agents given that in general it also correlates with an increase in therapeutic index, the ratio between the LD50 for a particular compound, and the levels required in order to achieve the desired therapeutic effect. However, one of the drawbacks of these developmental strategies is that they fend to select for compounds that are not optimal in terms of drug delivery properties, leading to impediments in moving candidate compounds to the later stages of development.
Thus, one of the limitations in newer approaches to development of novel pharmaceuticals is that new chemical entities may not always have the desired properties that would make them excellent candidates for oral administration, notwithstanding the fact that the active ingredient may possess significant therapeutic potential.
Recent experience has shown that many new APIs are poorly water-soluble and not well absorbed after administration (See for example: Charman & Charman, 2003; van Drooge et al., 2006). Limitations in the rate of solubilization and absorption will have a direct impact on bioavailability and pharmacokinetic performance of any compound. Thus, in many cases, it will be desirable to improve upon the solubility properties of an API in order to reduce the time before therapeutically effective levels are achieved in the patient, as well to improve the overall uptake of the pharmaceutical in the systemic-circulation, or whatever compartment the drug is intended to reach in order to exert its therapeutic effects.
The production of solid drug dispersions is one method available to improve solubility and dissolution of poor water-soluble drugs (Vasconcelos et al., 2007). The enhancement of solubility and dissolution may lead to the increase of bioavailability and/or permit the use of a reduced dose for drugs with poor water solubility. However, limitations of solid dispersion technology include, but are not limited by, laborious and expensive methods of preparation, reproducibility of physicochemical characteristics, difficulty in incorporating into formulation of dosage forms, scale-up of manufacturing process, and stability of the drug and vehicle.